565959
research-article2015
MSJ0010.1177/1352458514565959Multiple Sclerosis JournalCP Kamm, HP Mattle
MULTIPLE SCLEROSIS MSJ JOURNAL
Original Research Paper
Home-based training to improve manual dexterity in patients with multiple sclerosis: A randomized controlled trial
Multiple Sclerosis Journal 1–11 DOI: 10.1177/ 1352458514565959 © The Author(s), 2015. Reprints and permissions: http://www.sagepub.co.uk/ journalsPermissions.nav
Christian P Kamm, Heinrich P Mattle, René M Müri, Mirjam R Heldner, Verena Blatter, Sandrine Bartlome, Judith Lüthy, Debora Imboden, Giovanna Pedrazzini, Stephan Bohlhalter, Roger Hilfiker and Tim Vanbellingen
Abstract Background: Impaired manual dexterity is frequent and disabling in patients with multiple sclerosis (MS), affecting activities of daily living (ADL) and quality of life. Objective: We aimed to evaluate the effectiveness of a standardized, home-based training program to improve manual dexterity and dexterity-related ADL in MS patients. Methods: This was a randomized, rater-blinded controlled trial. Thirty-nine MS patients acknowledging impaired manual dexterity and having a pathological Coin Rotation Task (CRT), Nine Hole Peg Test (9HPT) or both were randomized 1:1 into two standardized training programs, the dexterity training program and the theraband training program. Patients trained five days per week in both programs over a period of 4 weeks. Primary outcome measures performed at baseline and after 4 weeks were the CRT, 9HPT and a dexterous-related ADL questionnaire. Secondary outcome measures were the Chedoke Arm and Hand Activity Inventory (CAHAI-8) and the JAMAR test. Results: The dexterity training program resulted in significant improvements in almost all outcome measures at study end compared with baseline. The theraband training program resulted in mostly non-significant improvements. Conclusion: The home-based dexterity training program significantly improved manual dexterity and dexterity-related ADL in moderately disabled MS patients. Trial Registration NCT01507636.
Keywords: Multiple sclerosis, manual dexterity, hand function, home-based training program, controlled clinical trials, randomized, manual therapies Date received: 5 August 2014; revised: 7 November 2014; 3 December 2014; accepted: 4 December 2014 Introduction Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system that is associated with various neurological sequelae.1 Impaired manual dexterity is frequent, affecting approximately three-quarters of patients with MS.2,3 It is a relevant handicap that impairs activities of daily living (ADL) and quality of life (QoL), and is associated with loss of work and the need to provide care.3–5 Despite its demonstrated importance, only limited research has been conducted on strategies to improve impaired manual dexterity in patients with MS. In a
systematic review, Spooren and colleagues (2012) identified 11 eligible studies on upper extremity training in MS patients.6 Only one of them, however, specifically addressed upper extremity function. In all other studies, upper extremity training was integrated into a total rehabilitation approach.6 In addition, a nonrandomized pilot study comparing two protocols of robot-based upper limb rehabilitation in 22 patients with MS demonstrated significant improvements of arm tremor, arm kinematics and functional ability in favor of the protocol with manipulative tasks.7 Recently, a single-group home-based sensory reeducation training program on hand sensibility and
Correspondence to: Christian Kamm Department of Neurology, Inselspital, Bern University Hospital, and University of Bern, Freiburgstrasse, Bern, 3010, Switzerland. [email protected] Christian P Kamm Heinrich P Mattle Mirjam R Heldner Verena Blatter Giovanna Pedrazzini Department of Neurology, Inselspital, Bern University Hospital, and University of Bern, Switzerland René M Müri Sandrine Bartlome Judith Lüthy Debora Imboden Division of Cognitive and Restorative Neurology, Department of Neurology, Inselspital, Bern University Hospital, and University of Bern, Switzerland Stephan Bohlhalter Neurology and Neurorehabilitation Center, Luzerner Kantonsspital, Switzerland Tim Vanbellingen Department of Neurology, Inselspital, Bern University Hospital, and University of Bern, Switzerland/Neurology and Neurorehabilitation Center, Luzerner Kantonsspital, Switzerland Roger Hilfiker HES-SO Valais-Wallis, School of Health Sciences, University of Applied Sciences and Arts Western Switzerland Valais, Sion, Switzerland
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Multiple Sclerosis Journal manual dexterity in 25 patients with MS showed no effect on sensory impairment, but suggested improvements in manual dexterity.8
to the treatment assignment. Patients were instructed not to reveal their training program during the final visit (= rater-blinded).
The aim of this study was to develop a standardized, feasible, convenient and cost-effective training program to improve manual dexterity in MS patients with subjectively and objectively impaired manual dexterity. For this purpose, a home-based dexterity training program predominantly focusing on in-hand manipulation of objects, that was adapted from a program showing efficacy in patients after stroke and traumatic brain injury (dexterity training program), was compared with a home-based training program predominantly focusing on arm and hand strength training (theraband training program) in a rater-blinded, randomized controlled single-center study.9–11
Each patient provided written informed consent, and the study was approved by the ethics committee Bern, Switzerland. The Trial Registration Identifier is NCT01507636 (clinicaltrials.gov).
Materials and methods Patients Patients with clinically isolated syndrome, relapsing– remitting MS, secondary progressive MS or primary progressive MS according to the 2010 McDonald’s criteria were recruited from our outpatient clinic.12 Patients had to acknowledge impaired manual dexterity upon asking and had to have at least on one hand a pathological Coin Rotation Task (CRT) with values above 19 seconds and/or a pathological Nine Hole Peg Test (9HPT) with values two standard deviations above the mean normal values published by Oxford et al. at screening.13–15 Main exclusion criteria were relapses and/or steroid treatment within the preceding 2 months, rapidly progressive MS and additional diseases or conditions apart from MS that affect manual dexterity or compromise the adequate performance of the study procedures. Study design This was a single-center, randomized controlled raterblinded study. All evaluations and instructions were performed in the hospital. Eligible patients were randomized 1:1 into the dexterity training or theraband training group in blocks of four using sealed envelopes. At baseline, demographic data and efficacy measures were collected and patients were instructed in their home-based training program by an occupational therapist or neurologist. Co-interventions such as ongoing physical or occupational therapies were continued unchanged during the study. Afterwards, patients in both groups trained 5 days per week (approx. 30 minutes per day) for 4 weeks. At study end, efficacy measures were repeated by an occupational therapist blinded
Study procedures Clinical characteristics. At baseline, demographic data, handedness, disease duration, date of MS diagnosis, MS type, medication history and medical history were collected. Neurologic examination including Expanded Disability Status Scale (EDSS) was performed at screening by a certified EDSS rater (neurostatus.net) within 6 weeks before study entry.16 To further characterize patients, items 5–7 of the scale for the assessment and rating of ataxia (SARA), the Modified Ashworth Scale (MAS) for spasticity, the Montreal Cognitive Assessment (MOCA) for cognition and the Fatigue Severity Scale (FSS) were performed.17–20 Hand strength was rated according to the Medical Research Council (MRC) scale that ranges from M0 (no muscle contraction) to M5 (normal power), and sensory hand function was rated by asking the patient if they had no (0 points), mild (1 point), moderate (2 points) or severe (3 points) sensory deficits.21 Primary outcome measures. All outcome measurements were performed at baseline and study end. Primary efficacy measurements included the CRT and 9HPT as performance-based tests, and a dexterousrelated ADL questionnaire as a patient-reported outcome measure.13–15,22 The CRT has been validated in assessing manual dexterity in several neurological disorders such as stroke,23 Parkinson’s disease and MS.14,24,25 Patients had to rotate a 50 Swiss Rappen coin (diameter: 18.20 mm; thickness: 1.25 mm; weight: 2.2 g) as fast as possible between their thumb, index and middle finger. The time to perform 20 half turns was measured twice on both hands and mean values were taken for each hand.13,14 Values of 18.75 seconds for the dominant and 19.25 seconds for the non-dominant hand were used as cut-off values for impaired manual dexterity as previously published.14 The 9HPT is reliable (ICC values 0.80–0.99), valid and sensitive in detecting impaired dexterity in patients with MS.26 Patients were seated at a table with a shallow container holding nine pegs and a
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CP Kamm, HP Mattle et al. plastic block with nine empty holes. All pegs had to be put one at a time into the holes and then removed again one at a time into the shallow container. The time to complete the task was recorded twice on both hands and mean values were taken for each hand.15 As a patient-recorded outcome measure for manual dexterity, an adapted version of a published dexterity questionnaire was used.27 The scaling was changed to a 4-point Likert scale as describe below; otherwise the original questionnaire was unchanged. It contains 24 questions divided into five subgroups (“washing/ grooming”; “dressing”; “meals and kitchen”; “everyday tasks”; “TV/CD/DVD”). For each question, patients had to state whether they had no problems (4 points), minor problems (3 points), major problems (2 points), or needed aid (1 point) to perform the task. Points were added in each subgroup and summed to one total score. The validity of this questionnaire to detect impaired dexterous skills in MS has been shown.14,22 Secondary outcome measures. The Chedoke Arm and Hand Activity Inventory (CAHAI-8) and the JAMAR dynamometer were used as secondary outcome measures.28,29 The CAHAI-8 is a performance-based test containing eight real-life upper limb functional tests (“pour a glass of water” etc.) rated on a 7-point quantitative scale, with higher scores indicating better performance. It has high inter-rater reliability, convergent and discriminant cross-sectional validity in patients with stroke.28 The hand-held JAMAR dynamometer (Sammons Preston Rolyan, 1000 Remington Blvd, Bolingbrook, IL, 60440) is a reliable (ICC values 0.85–0.98) and valid test to measure isometric grip strength in healthy subjects and MS patients.29 It was performed in an upright seating position with 90° flexion of the elbow next to the body. Mean values (kilograms force) of three maximum voluntary grip strength movements were taken for each hand. In addition, exercises 1–4 of the dexterity training program (see below) were performed in both groups and the number of achieved tasks in one minute was noted for each exercise. Home-based training programs. After baseline measurements patients were instructed into their homebased training programs by one occupational therapist (SB, JL, DI) or neurologist (CPK) with expertise in MS. Patients of both training groups trained 5 days
per week (approx. 30 minutes per day) for 4 weeks. All exercises were performed with both hands. Patients received a booklet explaining all exercises with pictures and a short text. This booklet contained a diary to document if an exercise was performed and, if applicable, the time needed to accomplish the exercise. Patients were contacted by an occupational therapist after 1 week of training asking whether there were any difficulties in performing the exercises. Dexterity training program. The dexterity program was adapted from a published Arm Ability Training program that showed high efficacy in improving manual dexterity and timed performance in dexterityrelated ADL in patients with mild arm paresis after stroke and traumatic brain injury.9,10 Patients had to perform six different exercises, illustrated in detail in Figure 1. Exercises 1–4 were performed at baseline as fast as possible and the number of achieved task in 1 minute was noted. At home, patients had to perform the achieved number at baseline as fast as possible, and note the time needed. Exercises 5 and 6 were performed without measuring the time. Theraband training program. Patients had to perform seven upper extremity strength-training exercises using a Theraband®, that are illustrated in detail in Figure 1. Theraband® exercises are commonly used in the rehabilitation of many diseases including MS.11 Patients had to note whether they performed the exercise or not. Sample size There were no previous studies that evaluated the effect of our training program or similar training programs on manual dexterity and especially the used primary endpoints in patients with MS. Therefore, the decision to include a total of 40 patients was based on previous randomized controlled trials that evaluated similar training programs on manual dexterity in other neurological diseases.9,10 In these studies a sample of 20 patients per group was necessary to achieve an 80% chance (power = 0.80) to observe a statistically significant (α = 0.05, two-sided) differential effect. Data analysis Descriptive statistics were used for baseline characteristics and results of outcome measurements. One-way ANOVA (continuous data) or chi-square statistic (nominal data) were used to investigate whether baseline variables differed between the two groups. Improvements within the groups from baseline (t0) to follow-up (t1) for
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Multiple Sclerosis Journal
Figure 1. Self-performed, home-based training programs.
each outcome measurement were analyzed using the dependent t-statistic. For the between-group differences, primary and secondary outcome scores were
analyzed using a series of covariance tests (ANCOVA) to measure changes over time. Baseline scores acted as covariates. All group comparisons were based on
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CP Kamm, HP Mattle et al. The changes of the efficacy endpoints from baseline (t0) to program end (t1) for each training group and the between-group differences are presented in Table 3.
Figure 2. Enrollment, allocation and follow-up of patients.
intention-to-treat-analysis. The Benjamini–Hochberg procedure was applied to control the false discovery rate.30 Two-sided 95% confidence intervals (CI) were calculated for the primary outcomes. In addition, Cohen’s d was calculated to evaluate effect size between the groups. Effect size is considered small, medium and large for d values above 0.2, 0.5 and 0.8 respectively.31 For all analyses the level of significance was set at p = 0.05 (two-tailed). Statistical analyses were performed using PASW for Windows (version 21.0; SPSS, Inc. Chicago, IL). Results From January to December 2012, 63 patients were assessed for eligibility of which 39 participated. In total, 20 patients were randomized into the dexterity training group and 19 patients into the theraband training group. One patient in the dexterity training group dropped out due to a relapse with left-sided hemiparesis. All other patients completed the study (Figure 2). Compliance to the training programs was good with an average of > 90% of performed exercises in both groups. Three patients in the dexterity training group and four patients in the theraband training group had existing non-specific occupational and/or physical therapies that were continued unchanged during the study. Patients’ baseline characteristics are presented in Table 1. The results of the baseline measurements are presented in Table 2. There were no significant differences regarding patients’ characteristics and measurements at baseline between the two groups.
Efficacy of dexterity training program With regard to the primary endpoints, the CRT improved significantly on both hands. The total score of the dexterity questionnaire and all subscores except “washing/grooming” and “dressing” improved significantly as well. Mean values of the 9HPT improved, however not significantly. With regard to the secondary endpoints, the CAHAI improved significantly as well as the JAMAR on the right side. In addition, all trained exercises 1–4 improved significantly (Table 3). Efficacy of theraband training program None of the primary and secondary endpoints improved significantly. There were significant improvements in most exercises 1–4 (Table 3). Dexterity training vs. theraband training program between-group comparisons Significant group differences in favor of the dexterity training program were found for one of the exercises 1–4. No significant differences were found for the primary and secondary endpoints, although improvements of absolute mean values were always higher in the dexterity training group except for the 9HPT of the right hand and the subscores “washing/grooming” and “dressing” of the dexterity questionnaire. In addition, effect sizes calculated with Cohen’s d showed mostly large effects for trained tasks and small and medium effects for the other outcome measures in favor of the dexterity training program (Table 3).31 Discussion The present study investigated the effectiveness of a standardized, home-based training program to improve manual dexterity and eventually dexterityrelated ADL in patients with MS. We performed a randomized, rater-blinded, controlled trial comparing two standardized 4-week home-based training programs focusing on different aspects on manual dexterity and arm and hand function. The dexterity training program predominantly consisted of fine motor dexterity exercises with in-hand manipulation of objects, whereas the theraband training program predominantly consisted of hand and arm strengthtraining exercises (Figure 1). Both groups were well matched with regard to baseline characteristics (Table 1) and baseline measurements (Table 2).
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Multiple Sclerosis Journal Table 1. Baseline characteristics. Characteristics
Dexterity training group
Theraband training group
p-value
n = 20
n = 19
Age (y) Gender, n (%) female Handedness, n (%) Right Disease duration (y) EDSS MS type, n (%) RRMS SPMS PPMS Immunomodulatory therapy, n (%) Interferon beta Glatiramer acetate Natalizumab Mitoxantron/Imurek No therapy SARA Right Left MAS Right Left Strength of the hands (MRC scale) right left Sensory deficits of the hands right left FSS MOCA
49.20 ± 10.87
51.89 ± 8.02
14 (70%)
12 (63%)
19 (95%) 15.38 ± 9.95 4.28 ± 1.48
18 (95%) 15.95 ± 9.68 4.82 ± 1.04
13 (65) 6 (30) 1 (5)
14 (74) 5 (26) 0
0.39 0.65 0.97 0.86 0.20 0.58 0.84
8 (40%) 1 (5%) 7 (35%) 1 (5%) 3 (15%)
9 (47%) 1 (5%) 6 (32%) 2 (11%) 1 (5%)
2.00 ± 1.86 2.60 ± 1.54
1.63 ± 1.42 1.95 ± 1.13
0.30 ± 0.57 0.55 ± 0.76
0.42 ± 0.69 0.47 ± 0.61
4.55 ± 0.61 4.40 ± 0.60
4.47 ± 0.51 4.58 ± 0.51
0.35 ± 0.75 0.60 ± 0.94 4.68 ± 1.39 25.55 ± 2.74
0.53 ± 0.70 0.53 ± 0.70 5.08 ± 1.05 25.47 ± 2.48
0.49 0.14 0.55 0.73 0.67 0.32 0.45 0.78 0.32 0.93
Values are mean ± SD or as otherwise indicated; SD: standard deviation; y: years; n: number of patients; EDSS: Expanded Disability Status Scale; RRMS: relapsing–remitting multiple sclerosis; SPMS: secondary progressive multiple sclerosis; PPMS: primary progressive multiple sclerosis; SARA: Scale for the Assessment and Rating of Ataxia; MAS: Modified Ashworth Scale; MRC: Medical Research Council; FSS: Fatigue Severity Scale; MOCA: Montreal Cognitive Assessment; ns: no significant difference.
After 4 weeks of training, the dexterity training program resulted in significant improvements in almost all outcome measures at study end compared with baseline. The CRT and JAMAR improved, indicating increased dexterous skills and grip strength, respectively, with a clinically meaningful improvement over 15% for the CRT.32 Furthermore, the CAHAI-8 as real-life upper limb functional tests and the dexterity questionnaire improved significantly, indicating a
positive effect on dexterity-related ADL. The trained exercises improved significantly as well, which can be explained by training effects. The dexterity training program was superior to the theraband training program with regard to higher absolute improvements in almost all endpoints that reached significance in one trained exercise, however in none of the primary and secondary endpoints.
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CP Kamm, HP Mattle et al. Table 2. Baseline measurements (t0). CRT (s) right left 9HPT (s) right left JAMAR (kg) right left Dexterity group exercises 1–4 (n) Finger tapping right left Crossing circles right left Turning metal discs right left Turning nuts on bolts right left CAHAI Dexterity questionnaire Total score Washing/grooming Dressing Meals and kitchen Everyday tasks Television and radio
Dexterity training group n = 20
Theraband training group n = 19
28.08 ± 13.82* 33.80 ± 17.88
30.82 ± 21.12 27.24 ± 8.37
30.21 ± 12.58 28.54 ± 8.14
28.59 ± 8.23 28.19 ± 5.33
24.78 ± 11.72 23.95 ± 7.77
26.58 ± 11.59 26.93 ± 10.92
22.40 ± 6.58 21.10 ± 4.17
23.68 ± 6.84 22.89 ± 5.16
71.85 ± 28.44 57.60 ± 19.03
68.26 ± 32.62 59.05 ± 21.42
35.95 ± 14.38 36.70 ± 13.69
33.84 ± 12.16 37.11 ± 8.99
1.58 ± 0.45 1.72 ± 0.51 52.15 ± 3.82
1.63 ± 0.64 1.48 ± 0.55 53.00 ± 2.79
85.85 ± 7.38 14.90 ± 1.21 10.20 ± 1.47 24.90 ± 2.73 21.20 ± 2.38 14.65 ± 1.73
82.58 ± 9.19 14.42 ± 1.85 9.05 ± 2.09 24.05 ± 2.57 21.00 ± 2.77 14.05 ± 1.62
p-value 0.64 0.15 0.64 0.88 0.62 0.33 0.55 0.24 0.72 0.82 0.63 0.91 0.76 0.18 0.43 0.23 0.35 0.06 0.33 0.81 0.27
Values are mean ± SD or as otherwise indicated; SD; standard deviation; n: number of patients; s: seconds; * 19 patients were analyzed because one patient could not perform the CRT on the right side due to severe dexterous difficulties; CRT: Coin Rotation Task; 9HPT: Nine Hole Peg Test; CAHAI: Chedoke Arm and Hand Activity Inventory; Dexterity Q: Dexterity questionnaire.
This lack of significance is due to mostly non-significant improvements of manual dexterity and dexterityrelated ADL in the theraband training group as well, and in this regard the low number of patients (Table 3). This is not surprising because the theraband training program is an established arm and hand function training program.11 Impaired manual dexterity in MS results from several neurological deficits such as ataxia, spasticity, paresis, sensory deficits or apraxia alone or in combination with each other, as well as de-conditioning.22 Despite focusing on different aspects on arm and hand function, both programs train several causes of impaired manual dexterity and aspects of its counterpart. This explains the positive
effect of the theraband training program on manual dexterity with regard to fine motor dexterity, as well as the superior effect of the dexterity training program on grip strength measured by the JAMAR. The latter is probably due to exercises 5 and 6 of the dexterity training program that contain kneading tasks that strengthen hand-grip. Furthermore, both programs probably improved physical de-conditioning of lessused upper extremities, explaining the strong effects in a very short time in some patients. In our opinion, the results are in favor of the dexterity program on manual dexterity and especially fine motor dexterity compared with the theraband training
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CRT (s) Right Left 9HPT (s) Right Left JAMAR (kg) Right Left Dexterity group Exercises 1–4 (n) Finger tapping Right Left Crossing circles Right Left Turning metal discs Right Left Turning nuts on bolts Right Left CAHAI Dexterity questionnaire Total score Washing/ grooming Dressing
0.02 0.03 0.38 0.12 0.02 0.38
0.0004 0.003
0.0004 0.0004
0.0004 0.0004
0.02 0.03 0.003
0.005 0.55 1.0
−6.36 ± 9.31 (−10.99 to −1.73)¶ −4.26 ± 7.83 (−8.04 to −0.49)
−1.51 ± 6.73 (–4.46 to 1.73) −1.28 ± 3.17 (−2.81 to 0.25)
2.25 ± 3.20 (0.70 to 3.79) 2.72 ± 5.01 (0.31 to 5.13)
7.74 ± 6.33 (4.69 to 10.79) 8.11 ± 8.89 (3.82 to 12.39)
19.95 ± 17.69 (11.42 to 28.47) 22.63 ± 19.08 (13.44 to 31.83)
10.90 ± 11.22 (5.49 to 16.3) 11.79 ± 9.48 (7.22 to 16.36)
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0.26 ± 0.41 (0.07 to 0.46) 0.30 ± 0.52 (0.05 to 0.55) 1.42 ± 1.54 (0.68 to 2.16)
3.37 ± 3.98 (1.45 to 5.28) 0.21 ± 1.40 (−0.46 to 0.88)
0.0 ± 1.0 (−0.48 to 0.48)
0.68 ± 1.64 (−0.10 to 1.47)
2.37 ± 5.73 (−0.39 to 5.13) 0.37 ± 1.21 (−0.22 to 0.95)
0.04 ± 0.37 (−0.14 to 0.21) 0.20 ± 0.34 (0.03 to 0.36) 0.95 ± 1.75 (0.11 to 1.79)
6.68 ± 7.96 (2.85 to 10.52) 6.21 ± 5.77 (3.43 to 8.99)
7.58 ± 14.94 (0.38 to 14.78) 3.90 ± 11.90 (−1.84 to 9.63)
2.90 ± 3.77 (1.09 to 4.71) 2.00 ± 3.25 (0.43 to 3.57)
0.75 ± 2.86 (−0.62 to 2.13) 0.91 ± 3.08 (−0.57 to 2.40)
−2.16 ± 6.01 (–5.06 to 0.74) −0.98 ± 2.63 (−2.25 to 0.28)
−4.37 ± 8.29 (−8.36 to 0.37) −1.92 ± 4.85 (–4.12 to 0.42)
Change (t1-t0)
Change (t1-t0) p-value+
Theraband training group n = 19
Dexterity training group n = 19
Table 3. Efficacy endpoints. Changes baseline to program end.
0.17
0.17 0.26
0.71 0.08 0.1
0.02 0.002
0.11 0.25
0.03 0.08
0.3 0.27
0.22 0.21
0.06 0.10
p-value#
0.68 (−0.21 to 1.58)
−1.00 (–4.24 to 2.24) 0.16 (−0.70 to 1.02)
−0.23 (−0.49 to 0.03) −0.10 (−0.39 to 0.19) −0.47 (−1.56 to 0.61)
−4.21 (−10.61 to 2.19) −5.58 (−10.74 to −0.42)
−12.37 (−23.14 to −1.60) −18.74 (−29.20 to −8.28)
−4.84 (−8.27 to −1.41) −6.11 (−10.51 to −1.70)
−1.49 (–3.49 to 0.51) −1.81 (–4.54 to 0.93)
−0.65 (–4.85 to 3.56) 0.30 (−1.62 to 2.21)
1.99 (–3.88 to 7.87) 2.34 (−1.94 to 6.63)
Group Difference Dexterity - Theraband
0.40 (−0.51 to 1.31)
−1.47 (–4.69 to 1.75) −0.04 (−0.77 to 0.68)
−0.22 (−0.47 to 0.04) −0.14 (−0.43 to 0.16) −0.31 (−1.37 to 0.74)
−4.17 (−10.69 to −2.35) −5.60 (−10.74 to −0.46)
−12.70 (−23.55 to −1.85) −18.51 (−29.04 to −7.98)
−4.21 (−7.44 to −0.98) −5.63 (−10.09 to −1.17)
−1.55 (–3.56 to 0.46) −1.49 (–4.24 to 1.26)
−0.49 (–4.71 to 3.74) 0.26 (−1.62 to 2.13)
2.79 (−0.88 to 6.47) 1.15 (−2.74 to 5.03)
Adjusted Group Difference Dexterity Theraband
0.48
0.48 0.91
0.24 0.48 0.62
0.38 0.11
0.1 0.02
0.1 0.1
0.27 0.46
0.87 0.87
0.26 0.55
p-value*
0.50
0.20 0.12
0.56 0.23 0.29
0.43 0.71
0.76 1.18
0.93 0.91
0.23 0.36 0.10 0.10 0.49 0.44
Cohen’s d
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0.02 0.02 0.03
1.11 ± 1.76 (0.26 to 1.95)
0.80 ± 1.27 (0.18 to 1.40)
p-value+
1.26 ± 1.85 (0.37 to 2.16)
Change (t1-t0)
Dexterity training group n = 19
0.16 ± 1.80 (−0.71 to 1.03)
0.53 ± 1.95 (−0.42 to 1.47)
0.63 ± 1.46 (−0.07 to 1.34)
Change (t1-t0)
Theraband training group n = 19
0.71
0.3
0.17
p-value#
−0.63 (−1.66 to 0.40)
−0.58 (−1.80 to 0.65)
−0.63 (−1.73 to 0.47)
Group Difference Dexterity - Theraband
−0.89 (−1.79 to 0.05)
−0.60 (−1.72 to 0.53)
−0.81 (−1.85 to 0.24)
Adjusted Group Difference Dexterity Theraband
0.16
0.46
0.27
p-value*
0.41
0.31
0.38
Cohen’s d
Values are mean ± SD or as otherwise indicated; n: number of patients; sec: seconds; CRT: Coin Rotation Task; 9HPT: Nine Hole Peg Test; AFT: Arm Function Training; CAHAI: Chedoke Arm and Hand Activity Inventory; Dexterity Q: Dexterity questionnaire; ¶n=18 (One patient could not perform the CRT on the right side due to severe dexterous difficulties); +p-value change baseline to program end Dexterity training group; #p-value change baseline to program end Theraband training group; *p-value change baseline to program end Dexterity training vs. Theraband training group; d: Cohen’s d. Adjusted Group Difference Dexterity – Theraband: This is the difference in the change of the outcome measure between both groups (Dexterity – Theraband group) controlled for the baseline value of the corresponding outcome measure.
Meals and kitchen Everyday tasks Television and radio
Table 3. (Continued)
CP Kamm, HP Mattle et al.
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Multiple Sclerosis Journal program. This is underlined by the calculated effect sizes (Cohen’s d) which were in favor of the dexterity training program (Table 3). The efficacy of the training program is remarkable, especially with regard to its practicability. Questioning patients and performing the CRT and/or 9HPT as dexterity assessments identifies patients suitable for training. The instruction is restricted to the explanation of the training program and takes 15–30 minutes, which can be done by an occupational or physical therapist. Further time-consuming individualized evaluations and instructions such as in “client-centered” rehabilitation programs are not necessary.33 The home-based training program allows frequent training independently of available hospital or community-based programs, at any time of the day. Patients with problems in transportation and patients who are inflexible time-wise, for example due to work, are able to perform the program as well. Finally, it is very cheap, with material costs below 10 Euros/ Dollars besides the staff costs for the instruction, and materials can be easily accessed in any hardware store. It can be applied as exclusive therapy or integrated in a multimodal therapeutic approach addressing several disabilities of MS patients in stationary, ambulatory or home-based training programs.34 Study limitations We did not evaluate the long-term effect of the training programs. Based on similar studies one can expect that positive effects are maintained for weeks to months without further training.35 However, designing training programs that evidentially improve manual dexterity over a long period of time would be of great interest and importance. Comparisons with control groups without training are problematic because they do not account for the placebo effect of any intervention, and were therefore not incorporated in the randomized controlled study. However, in an independent unmatched group of nine patients with MS that did not perform a training program, we found no significant differences for the all performed endpoints (CRT, 9HPT, JAMAR, dexterity group exercises 1–4, dexterity questionnaire) within an interval of 4 weeks. Although we expect the dexterity questionnaire to be sensitive in detecting changes over time, its responsiveness has to be defined in future studies. Finally, adherence and performance of the exercises was not sufficiently controlled, which is important – however, difficult – in home-based training programs. It could be achieved by self-performed video recordings by patients at home, which is, however, expensive and cumbersome.
Conclusions The standardized 4-week home-based dexterity training program significantly improved manual dexterity and dexterity-related ADL in moderately disabled MS patients with subjectively and objectively impaired manual dexterity. It can be easily applied and performed independently of hospital or communitybased training programs, as well as in patients with transportation problems and time-wise inflexible patients. Therefore, it should be considered in MS patients with impaired manual dexterity. Conflict of interest None declared. Funding The study was supported by a research grant of Bayer (Schweiz) AG.
References 1. Kamm CP, Uitdehaag BM and Polman CH. Multiple sclerosis: Current knowledge and future outlook. Eur Neurol 2014; 72: 132–141. 2. Johansson S, Ytterberg C, Claesson IM, et al. High concurrent presence of disability in multiple sclerosis. Associations with perceived health. J Neurol 2007; 254: 767–773. 3. Chruzander C, Johansson S, Gottberg K, et al. A 10-year follow-up of a population-based study of people with multiple sclerosis in Stockholm, Sweden: Changes in disability and the value of different factors in predicting disability and mortality. J Neurol Sci 2013; 332: 121–127. 4. Kierkegaard M, Einarsson U, Gottberg K, et al. The relationship between walking, manual dexterity, cognition and activity/participation in persons with multiple sclerosis. Mult Scler 2012; 18: 639–646. 5. Abbas D, Gehanno JF, Caillard JF, et al. Characteristics of patients suffering from multiple sclerosis according to professional situation. Ann Readapt Med Phys 2008; 51: 386–393. 6. Spooren AI, Timmermans AA and Seelen HA. Motor training programs of arm and hand in patients with MS according to different levels of the ICF: A systematic review. BMC Neurol 2012; 12: 49. 7. Carpinella I, Cattaneo D, Bertoni R, et al. Robot training of upper limb in multiple sclerosis: Comparing protocols with or without manipulative task components. IEEE Trans Neural Syst Rehabil Eng 2012; 20: 351–360. 8. Kalron A, Greenberg-Abrahami M, Gelav S, et al. Effects of a new sensory re-education training tool on
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CP Kamm, HP Mattle et al. hand sensibility and manual dexterity in people with multiple sclerosis. NeuroRehabilitation 2013; 32: 943–948. 9. Platz T, Winter T, Müller N, et al. Arm ability training for stroke and traumatic brain injury patients with mild arm paresis: A single-blind, randomized, controlled trial. Arch Phys Med Rehabil 2001; 82: 961–968. 10. Platz T. IOT- Impairement-Oriented Training, Schädigungs-orientiertes Training. Baden Baden: Deutscher Wissenschafts-Verlag (DWV), 2006. 11. Romberg A, Virtanen A, Ruutiainen J, et al. Effects of a 6-month exercise program on patients with multiple sclerosis: A randomized study. Neurology 2004; 63: 2034–2038. 12. Polman CH, Reingold SC, Banwell B, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 2011; 69: 292–302. 13. Mendoza JE, Apostolos GT, Humphreys JD, et al. Coin Rotation Task (CRT): A new test of motor dexterity. Arch Clin Neuropsychol 2009; 24: 287–292. 14. Heldner MR, Vanbellingen T, Bohlhalter S, et al. The Coin Rotation Task: A valid test for manual dexterity in multiple sclerosis. Phys Ther 2014; Jun 19. [Epub ahead of print] 15. Oxford Grice K, Vogel KA, Le V, et al. Adult norms for a commercially available Nine Hole Peg Test for finger dexterity. Am J Occup Ther 2003; 57: 570–573. 16. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: An Expanded Disability Status Scale (EDSS). Neurology 1983; 33: 1444–1452. 17. Schmitz-Hübsch T, du Montcel ST, Baliko L, et al. Scale for the assessment and rating of ataxia: Development of a new clinical scale. Neurology 2006; 66: 1717–1720. Erratum in Neurology 2006; 67: 299.
22. Kamm CP, Heldner MR, Vanbellingen T, et al. Limb apraxia in multiple sclerosis: Prevalence and impact on manual dexterity and activities of daily living. Arch Phys Med Rehabil 2012; 93: 1081–1085. 23. Hanna-Pladdy B, Mendoza JE, Apostolos GT, et al. Lateralised motor control: Hemispheric damage and the loss of deftness. J Neurol Neurosurg Psychiatry 2002; 73: 574–577. 24. Gebhardt A, Vanbellingen T, Baronti F, et al. Poor dopaminergic response of impaired dexterity in Parkinson’s disease: Bradykinesia or limb kinetic apraxia? Mov Disord 2008; 23:1701–1706. 25. Vanbellingen T, Kersten B, Bellion M, et al. Impaired finger dexterity in Parkinson’s disease is associated with praxis function. Brain Cogn 2011; 77: 48–52. 26. Yancosek KE and Howell DJ. A narrative review of dexterity assessments. Hand Ther 2009; 22: 258–269. 27. Sunderland A. Recovery of ipsilateral dexterity after stroke. Stroke 2000; 31: 430–433. 28. Barreca SR, Stratford PW, Lambert CL, et al. Test-retest reliability, validity, and sensitivity of the Chedoke arm and hand activity inventory: A new measure of upper-limb function for survivors of stroke. Arch Phys Med Rehabil 2005; 86: 1616–1622. 29. Paltamaa J, West H, Sarasoja T, et al. Reliability of physical functioning measures in ambulatory subjects with MS. Physiother Res Int 2005; 10: 93–109. 30. Benjamini Y and Hochberg Y. Controlling the false discovery rate: A practical and powerful approach to multiple testing. J Royal Stat Soc 1995; 57: 289–300. 31. Cohen J. Quantitative measures in psychology. Psychol Bull 1992; 1: 155–159.
18. Bohannon RW and Smith MB. Interrater reliability of a Modified Ashworth Scale of muscle spasticity. Phys Ther 1987; 67: 206–207.
32. Rodgers H, Shaw L, Price C, et al. Study design and methods of the BoTULS trial: A randomized controlled trial to evaluate the clinical effect and cost effectiveness of treating upper limb spasticity due to stroke with botulinum toxin type A. Trials 2008; 9: 59.
19. Nasreddine ZS, Phillips NA, Bédirian V, et al. The Montreal Cognitive Assessment, MoCA: A brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005; 53: 695–699.
33. Khan F, Pallant JF, Brand C, et al. Effectiveness of rehabilitation intervention in persons with multiple sclerosis: A randomised controlled trial. J Neurol Neurosurg Psychiatry 2008; 79: 1230–1235.
20. Krupp LB, LaRocca NG, Muir-Nash J, et al. The fatigue severity scale. Application to patients with multiple sclerosis and systemic lupus erythematosus. Arch Neurol 1989; 46: 1121–1123.
34. Crayton H, Heyman RA and Rossman HS. A multimodal approach to managing the symptoms of multiple sclerosis. Neurology 2004; 14: 12–18.
21. Medical Research Council. Aids to the examination of the peripheral nervous system, Memorandum no. 45. London: Her Majesty’s Stationery Office, 1981.
35. Patti F, Ciancio MR, Cacopardo M, et al. Effects of a short outpatient rehabilitation treatment on disability of multiple sclerosis patients – a randomised controlled trial. J Neurol 2003; 250: 861–866.
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research-article2015
MSJ0010.1177/1352458514565959Multiple Sclerosis JournalCP Kamm, HP Mattle
MULTIPLE SCLEROSIS MSJ JOURNAL
Original Research Paper
Home-based training to improve manual dexterity in patients with multiple sclerosis: A randomized controlled trial
Multiple Sclerosis Journal 1–11 DOI: 10.1177/ 1352458514565959 © The Author(s), 2015. Reprints and permissions: http://www.sagepub.co.uk/ journalsPermissions.nav
Christian P Kamm, Heinrich P Mattle, René M Müri, Mirjam R Heldner, Verena Blatter, Sandrine Bartlome, Judith Lüthy, Debora Imboden, Giovanna Pedrazzini, Stephan Bohlhalter, Roger Hilfiker and Tim Vanbellingen
Abstract Background: Impaired manual dexterity is frequent and disabling in patients with multiple sclerosis (MS), affecting activities of daily living (ADL) and quality of life. Objective: We aimed to evaluate the effectiveness of a standardized, home-based training program to improve manual dexterity and dexterity-related ADL in MS patients. Methods: This was a randomized, rater-blinded controlled trial. Thirty-nine MS patients acknowledging impaired manual dexterity and having a pathological Coin Rotation Task (CRT), Nine Hole Peg Test (9HPT) or both were randomized 1:1 into two standardized training programs, the dexterity training program and the theraband training program. Patients trained five days per week in both programs over a period of 4 weeks. Primary outcome measures performed at baseline and after 4 weeks were the CRT, 9HPT and a dexterous-related ADL questionnaire. Secondary outcome measures were the Chedoke Arm and Hand Activity Inventory (CAHAI-8) and the JAMAR test. Results: The dexterity training program resulted in significant improvements in almost all outcome measures at study end compared with baseline. The theraband training program resulted in mostly non-significant improvements. Conclusion: The home-based dexterity training program significantly improved manual dexterity and dexterity-related ADL in moderately disabled MS patients. Trial Registration NCT01507636.
Keywords: Multiple sclerosis, manual dexterity, hand function, home-based training program, controlled clinical trials, randomized, manual therapies Date received: 5 August 2014; revised: 7 November 2014; 3 December 2014; accepted: 4 December 2014 Introduction Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system that is associated with various neurological sequelae.1 Impaired manual dexterity is frequent, affecting approximately three-quarters of patients with MS.2,3 It is a relevant handicap that impairs activities of daily living (ADL) and quality of life (QoL), and is associated with loss of work and the need to provide care.3–5 Despite its demonstrated importance, only limited research has been conducted on strategies to improve impaired manual dexterity in patients with MS. In a
systematic review, Spooren and colleagues (2012) identified 11 eligible studies on upper extremity training in MS patients.6 Only one of them, however, specifically addressed upper extremity function. In all other studies, upper extremity training was integrated into a total rehabilitation approach.6 In addition, a nonrandomized pilot study comparing two protocols of robot-based upper limb rehabilitation in 22 patients with MS demonstrated significant improvements of arm tremor, arm kinematics and functional ability in favor of the protocol with manipulative tasks.7 Recently, a single-group home-based sensory reeducation training program on hand sensibility and
Correspondence to: Christian Kamm Department of Neurology, Inselspital, Bern University Hospital, and University of Bern, Freiburgstrasse, Bern, 3010, Switzerland. [email protected] Christian P Kamm Heinrich P Mattle Mirjam R Heldner Verena Blatter Giovanna Pedrazzini Department of Neurology, Inselspital, Bern University Hospital, and University of Bern, Switzerland René M Müri Sandrine Bartlome Judith Lüthy Debora Imboden Division of Cognitive and Restorative Neurology, Department of Neurology, Inselspital, Bern University Hospital, and University of Bern, Switzerland Stephan Bohlhalter Neurology and Neurorehabilitation Center, Luzerner Kantonsspital, Switzerland Tim Vanbellingen Department of Neurology, Inselspital, Bern University Hospital, and University of Bern, Switzerland/Neurology and Neurorehabilitation Center, Luzerner Kantonsspital, Switzerland Roger Hilfiker HES-SO Valais-Wallis, School of Health Sciences, University of Applied Sciences and Arts Western Switzerland Valais, Sion, Switzerland
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Multiple Sclerosis Journal manual dexterity in 25 patients with MS showed no effect on sensory impairment, but suggested improvements in manual dexterity.8
to the treatment assignment. Patients were instructed not to reveal their training program during the final visit (= rater-blinded).
The aim of this study was to develop a standardized, feasible, convenient and cost-effective training program to improve manual dexterity in MS patients with subjectively and objectively impaired manual dexterity. For this purpose, a home-based dexterity training program predominantly focusing on in-hand manipulation of objects, that was adapted from a program showing efficacy in patients after stroke and traumatic brain injury (dexterity training program), was compared with a home-based training program predominantly focusing on arm and hand strength training (theraband training program) in a rater-blinded, randomized controlled single-center study.9–11
Each patient provided written informed consent, and the study was approved by the ethics committee Bern, Switzerland. The Trial Registration Identifier is NCT01507636 (clinicaltrials.gov).
Materials and methods Patients Patients with clinically isolated syndrome, relapsing– remitting MS, secondary progressive MS or primary progressive MS according to the 2010 McDonald’s criteria were recruited from our outpatient clinic.12 Patients had to acknowledge impaired manual dexterity upon asking and had to have at least on one hand a pathological Coin Rotation Task (CRT) with values above 19 seconds and/or a pathological Nine Hole Peg Test (9HPT) with values two standard deviations above the mean normal values published by Oxford et al. at screening.13–15 Main exclusion criteria were relapses and/or steroid treatment within the preceding 2 months, rapidly progressive MS and additional diseases or conditions apart from MS that affect manual dexterity or compromise the adequate performance of the study procedures. Study design This was a single-center, randomized controlled raterblinded study. All evaluations and instructions were performed in the hospital. Eligible patients were randomized 1:1 into the dexterity training or theraband training group in blocks of four using sealed envelopes. At baseline, demographic data and efficacy measures were collected and patients were instructed in their home-based training program by an occupational therapist or neurologist. Co-interventions such as ongoing physical or occupational therapies were continued unchanged during the study. Afterwards, patients in both groups trained 5 days per week (approx. 30 minutes per day) for 4 weeks. At study end, efficacy measures were repeated by an occupational therapist blinded
Study procedures Clinical characteristics. At baseline, demographic data, handedness, disease duration, date of MS diagnosis, MS type, medication history and medical history were collected. Neurologic examination including Expanded Disability Status Scale (EDSS) was performed at screening by a certified EDSS rater (neurostatus.net) within 6 weeks before study entry.16 To further characterize patients, items 5–7 of the scale for the assessment and rating of ataxia (SARA), the Modified Ashworth Scale (MAS) for spasticity, the Montreal Cognitive Assessment (MOCA) for cognition and the Fatigue Severity Scale (FSS) were performed.17–20 Hand strength was rated according to the Medical Research Council (MRC) scale that ranges from M0 (no muscle contraction) to M5 (normal power), and sensory hand function was rated by asking the patient if they had no (0 points), mild (1 point), moderate (2 points) or severe (3 points) sensory deficits.21 Primary outcome measures. All outcome measurements were performed at baseline and study end. Primary efficacy measurements included the CRT and 9HPT as performance-based tests, and a dexterousrelated ADL questionnaire as a patient-reported outcome measure.13–15,22 The CRT has been validated in assessing manual dexterity in several neurological disorders such as stroke,23 Parkinson’s disease and MS.14,24,25 Patients had to rotate a 50 Swiss Rappen coin (diameter: 18.20 mm; thickness: 1.25 mm; weight: 2.2 g) as fast as possible between their thumb, index and middle finger. The time to perform 20 half turns was measured twice on both hands and mean values were taken for each hand.13,14 Values of 18.75 seconds for the dominant and 19.25 seconds for the non-dominant hand were used as cut-off values for impaired manual dexterity as previously published.14 The 9HPT is reliable (ICC values 0.80–0.99), valid and sensitive in detecting impaired dexterity in patients with MS.26 Patients were seated at a table with a shallow container holding nine pegs and a
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CP Kamm, HP Mattle et al. plastic block with nine empty holes. All pegs had to be put one at a time into the holes and then removed again one at a time into the shallow container. The time to complete the task was recorded twice on both hands and mean values were taken for each hand.15 As a patient-recorded outcome measure for manual dexterity, an adapted version of a published dexterity questionnaire was used.27 The scaling was changed to a 4-point Likert scale as describe below; otherwise the original questionnaire was unchanged. It contains 24 questions divided into five subgroups (“washing/ grooming”; “dressing”; “meals and kitchen”; “everyday tasks”; “TV/CD/DVD”). For each question, patients had to state whether they had no problems (4 points), minor problems (3 points), major problems (2 points), or needed aid (1 point) to perform the task. Points were added in each subgroup and summed to one total score. The validity of this questionnaire to detect impaired dexterous skills in MS has been shown.14,22 Secondary outcome measures. The Chedoke Arm and Hand Activity Inventory (CAHAI-8) and the JAMAR dynamometer were used as secondary outcome measures.28,29 The CAHAI-8 is a performance-based test containing eight real-life upper limb functional tests (“pour a glass of water” etc.) rated on a 7-point quantitative scale, with higher scores indicating better performance. It has high inter-rater reliability, convergent and discriminant cross-sectional validity in patients with stroke.28 The hand-held JAMAR dynamometer (Sammons Preston Rolyan, 1000 Remington Blvd, Bolingbrook, IL, 60440) is a reliable (ICC values 0.85–0.98) and valid test to measure isometric grip strength in healthy subjects and MS patients.29 It was performed in an upright seating position with 90° flexion of the elbow next to the body. Mean values (kilograms force) of three maximum voluntary grip strength movements were taken for each hand. In addition, exercises 1–4 of the dexterity training program (see below) were performed in both groups and the number of achieved tasks in one minute was noted for each exercise. Home-based training programs. After baseline measurements patients were instructed into their homebased training programs by one occupational therapist (SB, JL, DI) or neurologist (CPK) with expertise in MS. Patients of both training groups trained 5 days
per week (approx. 30 minutes per day) for 4 weeks. All exercises were performed with both hands. Patients received a booklet explaining all exercises with pictures and a short text. This booklet contained a diary to document if an exercise was performed and, if applicable, the time needed to accomplish the exercise. Patients were contacted by an occupational therapist after 1 week of training asking whether there were any difficulties in performing the exercises. Dexterity training program. The dexterity program was adapted from a published Arm Ability Training program that showed high efficacy in improving manual dexterity and timed performance in dexterityrelated ADL in patients with mild arm paresis after stroke and traumatic brain injury.9,10 Patients had to perform six different exercises, illustrated in detail in Figure 1. Exercises 1–4 were performed at baseline as fast as possible and the number of achieved task in 1 minute was noted. At home, patients had to perform the achieved number at baseline as fast as possible, and note the time needed. Exercises 5 and 6 were performed without measuring the time. Theraband training program. Patients had to perform seven upper extremity strength-training exercises using a Theraband®, that are illustrated in detail in Figure 1. Theraband® exercises are commonly used in the rehabilitation of many diseases including MS.11 Patients had to note whether they performed the exercise or not. Sample size There were no previous studies that evaluated the effect of our training program or similar training programs on manual dexterity and especially the used primary endpoints in patients with MS. Therefore, the decision to include a total of 40 patients was based on previous randomized controlled trials that evaluated similar training programs on manual dexterity in other neurological diseases.9,10 In these studies a sample of 20 patients per group was necessary to achieve an 80% chance (power = 0.80) to observe a statistically significant (α = 0.05, two-sided) differential effect. Data analysis Descriptive statistics were used for baseline characteristics and results of outcome measurements. One-way ANOVA (continuous data) or chi-square statistic (nominal data) were used to investigate whether baseline variables differed between the two groups. Improvements within the groups from baseline (t0) to follow-up (t1) for
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Multiple Sclerosis Journal
Figure 1. Self-performed, home-based training programs.
each outcome measurement were analyzed using the dependent t-statistic. For the between-group differences, primary and secondary outcome scores were
analyzed using a series of covariance tests (ANCOVA) to measure changes over time. Baseline scores acted as covariates. All group comparisons were based on
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CP Kamm, HP Mattle et al. The changes of the efficacy endpoints from baseline (t0) to program end (t1) for each training group and the between-group differences are presented in Table 3.
Figure 2. Enrollment, allocation and follow-up of patients.
intention-to-treat-analysis. The Benjamini–Hochberg procedure was applied to control the false discovery rate.30 Two-sided 95% confidence intervals (CI) were calculated for the primary outcomes. In addition, Cohen’s d was calculated to evaluate effect size between the groups. Effect size is considered small, medium and large for d values above 0.2, 0.5 and 0.8 respectively.31 For all analyses the level of significance was set at p = 0.05 (two-tailed). Statistical analyses were performed using PASW for Windows (version 21.0; SPSS, Inc. Chicago, IL). Results From January to December 2012, 63 patients were assessed for eligibility of which 39 participated. In total, 20 patients were randomized into the dexterity training group and 19 patients into the theraband training group. One patient in the dexterity training group dropped out due to a relapse with left-sided hemiparesis. All other patients completed the study (Figure 2). Compliance to the training programs was good with an average of > 90% of performed exercises in both groups. Three patients in the dexterity training group and four patients in the theraband training group had existing non-specific occupational and/or physical therapies that were continued unchanged during the study. Patients’ baseline characteristics are presented in Table 1. The results of the baseline measurements are presented in Table 2. There were no significant differences regarding patients’ characteristics and measurements at baseline between the two groups.
Efficacy of dexterity training program With regard to the primary endpoints, the CRT improved significantly on both hands. The total score of the dexterity questionnaire and all subscores except “washing/grooming” and “dressing” improved significantly as well. Mean values of the 9HPT improved, however not significantly. With regard to the secondary endpoints, the CAHAI improved significantly as well as the JAMAR on the right side. In addition, all trained exercises 1–4 improved significantly (Table 3). Efficacy of theraband training program None of the primary and secondary endpoints improved significantly. There were significant improvements in most exercises 1–4 (Table 3). Dexterity training vs. theraband training program between-group comparisons Significant group differences in favor of the dexterity training program were found for one of the exercises 1–4. No significant differences were found for the primary and secondary endpoints, although improvements of absolute mean values were always higher in the dexterity training group except for the 9HPT of the right hand and the subscores “washing/grooming” and “dressing” of the dexterity questionnaire. In addition, effect sizes calculated with Cohen’s d showed mostly large effects for trained tasks and small and medium effects for the other outcome measures in favor of the dexterity training program (Table 3).31 Discussion The present study investigated the effectiveness of a standardized, home-based training program to improve manual dexterity and eventually dexterityrelated ADL in patients with MS. We performed a randomized, rater-blinded, controlled trial comparing two standardized 4-week home-based training programs focusing on different aspects on manual dexterity and arm and hand function. The dexterity training program predominantly consisted of fine motor dexterity exercises with in-hand manipulation of objects, whereas the theraband training program predominantly consisted of hand and arm strengthtraining exercises (Figure 1). Both groups were well matched with regard to baseline characteristics (Table 1) and baseline measurements (Table 2).
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Multiple Sclerosis Journal Table 1. Baseline characteristics. Characteristics
Dexterity training group
Theraband training group
p-value
n = 20
n = 19
Age (y) Gender, n (%) female Handedness, n (%) Right Disease duration (y) EDSS MS type, n (%) RRMS SPMS PPMS Immunomodulatory therapy, n (%) Interferon beta Glatiramer acetate Natalizumab Mitoxantron/Imurek No therapy SARA Right Left MAS Right Left Strength of the hands (MRC scale) right left Sensory deficits of the hands right left FSS MOCA
49.20 ± 10.87
51.89 ± 8.02
14 (70%)
12 (63%)
19 (95%) 15.38 ± 9.95 4.28 ± 1.48
18 (95%) 15.95 ± 9.68 4.82 ± 1.04
13 (65) 6 (30) 1 (5)
14 (74) 5 (26) 0
0.39 0.65 0.97 0.86 0.20 0.58 0.84
8 (40%) 1 (5%) 7 (35%) 1 (5%) 3 (15%)
9 (47%) 1 (5%) 6 (32%) 2 (11%) 1 (5%)
2.00 ± 1.86 2.60 ± 1.54
1.63 ± 1.42 1.95 ± 1.13
0.30 ± 0.57 0.55 ± 0.76
0.42 ± 0.69 0.47 ± 0.61
4.55 ± 0.61 4.40 ± 0.60
4.47 ± 0.51 4.58 ± 0.51
0.35 ± 0.75 0.60 ± 0.94 4.68 ± 1.39 25.55 ± 2.74
0.53 ± 0.70 0.53 ± 0.70 5.08 ± 1.05 25.47 ± 2.48
0.49 0.14 0.55 0.73 0.67 0.32 0.45 0.78 0.32 0.93
Values are mean ± SD or as otherwise indicated; SD: standard deviation; y: years; n: number of patients; EDSS: Expanded Disability Status Scale; RRMS: relapsing–remitting multiple sclerosis; SPMS: secondary progressive multiple sclerosis; PPMS: primary progressive multiple sclerosis; SARA: Scale for the Assessment and Rating of Ataxia; MAS: Modified Ashworth Scale; MRC: Medical Research Council; FSS: Fatigue Severity Scale; MOCA: Montreal Cognitive Assessment; ns: no significant difference.
After 4 weeks of training, the dexterity training program resulted in significant improvements in almost all outcome measures at study end compared with baseline. The CRT and JAMAR improved, indicating increased dexterous skills and grip strength, respectively, with a clinically meaningful improvement over 15% for the CRT.32 Furthermore, the CAHAI-8 as real-life upper limb functional tests and the dexterity questionnaire improved significantly, indicating a
positive effect on dexterity-related ADL. The trained exercises improved significantly as well, which can be explained by training effects. The dexterity training program was superior to the theraband training program with regard to higher absolute improvements in almost all endpoints that reached significance in one trained exercise, however in none of the primary and secondary endpoints.
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CP Kamm, HP Mattle et al. Table 2. Baseline measurements (t0). CRT (s) right left 9HPT (s) right left JAMAR (kg) right left Dexterity group exercises 1–4 (n) Finger tapping right left Crossing circles right left Turning metal discs right left Turning nuts on bolts right left CAHAI Dexterity questionnaire Total score Washing/grooming Dressing Meals and kitchen Everyday tasks Television and radio
Dexterity training group n = 20
Theraband training group n = 19
28.08 ± 13.82* 33.80 ± 17.88
30.82 ± 21.12 27.24 ± 8.37
30.21 ± 12.58 28.54 ± 8.14
28.59 ± 8.23 28.19 ± 5.33
24.78 ± 11.72 23.95 ± 7.77
26.58 ± 11.59 26.93 ± 10.92
22.40 ± 6.58 21.10 ± 4.17
23.68 ± 6.84 22.89 ± 5.16
71.85 ± 28.44 57.60 ± 19.03
68.26 ± 32.62 59.05 ± 21.42
35.95 ± 14.38 36.70 ± 13.69
33.84 ± 12.16 37.11 ± 8.99
1.58 ± 0.45 1.72 ± 0.51 52.15 ± 3.82
1.63 ± 0.64 1.48 ± 0.55 53.00 ± 2.79
85.85 ± 7.38 14.90 ± 1.21 10.20 ± 1.47 24.90 ± 2.73 21.20 ± 2.38 14.65 ± 1.73
82.58 ± 9.19 14.42 ± 1.85 9.05 ± 2.09 24.05 ± 2.57 21.00 ± 2.77 14.05 ± 1.62
p-value 0.64 0.15 0.64 0.88 0.62 0.33 0.55 0.24 0.72 0.82 0.63 0.91 0.76 0.18 0.43 0.23 0.35 0.06 0.33 0.81 0.27
Values are mean ± SD or as otherwise indicated; SD; standard deviation; n: number of patients; s: seconds; * 19 patients were analyzed because one patient could not perform the CRT on the right side due to severe dexterous difficulties; CRT: Coin Rotation Task; 9HPT: Nine Hole Peg Test; CAHAI: Chedoke Arm and Hand Activity Inventory; Dexterity Q: Dexterity questionnaire.
This lack of significance is due to mostly non-significant improvements of manual dexterity and dexterityrelated ADL in the theraband training group as well, and in this regard the low number of patients (Table 3). This is not surprising because the theraband training program is an established arm and hand function training program.11 Impaired manual dexterity in MS results from several neurological deficits such as ataxia, spasticity, paresis, sensory deficits or apraxia alone or in combination with each other, as well as de-conditioning.22 Despite focusing on different aspects on arm and hand function, both programs train several causes of impaired manual dexterity and aspects of its counterpart. This explains the positive
effect of the theraband training program on manual dexterity with regard to fine motor dexterity, as well as the superior effect of the dexterity training program on grip strength measured by the JAMAR. The latter is probably due to exercises 5 and 6 of the dexterity training program that contain kneading tasks that strengthen hand-grip. Furthermore, both programs probably improved physical de-conditioning of lessused upper extremities, explaining the strong effects in a very short time in some patients. In our opinion, the results are in favor of the dexterity program on manual dexterity and especially fine motor dexterity compared with the theraband training
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CRT (s) Right Left 9HPT (s) Right Left JAMAR (kg) Right Left Dexterity group Exercises 1–4 (n) Finger tapping Right Left Crossing circles Right Left Turning metal discs Right Left Turning nuts on bolts Right Left CAHAI Dexterity questionnaire Total score Washing/ grooming Dressing
0.02 0.03 0.38 0.12 0.02 0.38
0.0004 0.003
0.0004 0.0004
0.0004 0.0004
0.02 0.03 0.003
0.005 0.55 1.0
−6.36 ± 9.31 (−10.99 to −1.73)¶ −4.26 ± 7.83 (−8.04 to −0.49)
−1.51 ± 6.73 (–4.46 to 1.73) −1.28 ± 3.17 (−2.81 to 0.25)
2.25 ± 3.20 (0.70 to 3.79) 2.72 ± 5.01 (0.31 to 5.13)
7.74 ± 6.33 (4.69 to 10.79) 8.11 ± 8.89 (3.82 to 12.39)
19.95 ± 17.69 (11.42 to 28.47) 22.63 ± 19.08 (13.44 to 31.83)
10.90 ± 11.22 (5.49 to 16.3) 11.79 ± 9.48 (7.22 to 16.36)
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0.26 ± 0.41 (0.07 to 0.46) 0.30 ± 0.52 (0.05 to 0.55) 1.42 ± 1.54 (0.68 to 2.16)
3.37 ± 3.98 (1.45 to 5.28) 0.21 ± 1.40 (−0.46 to 0.88)
0.0 ± 1.0 (−0.48 to 0.48)
0.68 ± 1.64 (−0.10 to 1.47)
2.37 ± 5.73 (−0.39 to 5.13) 0.37 ± 1.21 (−0.22 to 0.95)
0.04 ± 0.37 (−0.14 to 0.21) 0.20 ± 0.34 (0.03 to 0.36) 0.95 ± 1.75 (0.11 to 1.79)
6.68 ± 7.96 (2.85 to 10.52) 6.21 ± 5.77 (3.43 to 8.99)
7.58 ± 14.94 (0.38 to 14.78) 3.90 ± 11.90 (−1.84 to 9.63)
2.90 ± 3.77 (1.09 to 4.71) 2.00 ± 3.25 (0.43 to 3.57)
0.75 ± 2.86 (−0.62 to 2.13) 0.91 ± 3.08 (−0.57 to 2.40)
−2.16 ± 6.01 (–5.06 to 0.74) −0.98 ± 2.63 (−2.25 to 0.28)
−4.37 ± 8.29 (−8.36 to 0.37) −1.92 ± 4.85 (–4.12 to 0.42)
Change (t1-t0)
Change (t1-t0) p-value+
Theraband training group n = 19
Dexterity training group n = 19
Table 3. Efficacy endpoints. Changes baseline to program end.
0.17
0.17 0.26
0.71 0.08 0.1
0.02 0.002
0.11 0.25
0.03 0.08
0.3 0.27
0.22 0.21
0.06 0.10
p-value#
0.68 (−0.21 to 1.58)
−1.00 (–4.24 to 2.24) 0.16 (−0.70 to 1.02)
−0.23 (−0.49 to 0.03) −0.10 (−0.39 to 0.19) −0.47 (−1.56 to 0.61)
−4.21 (−10.61 to 2.19) −5.58 (−10.74 to −0.42)
−12.37 (−23.14 to −1.60) −18.74 (−29.20 to −8.28)
−4.84 (−8.27 to −1.41) −6.11 (−10.51 to −1.70)
−1.49 (–3.49 to 0.51) −1.81 (–4.54 to 0.93)
−0.65 (–4.85 to 3.56) 0.30 (−1.62 to 2.21)
1.99 (–3.88 to 7.87) 2.34 (−1.94 to 6.63)
Group Difference Dexterity - Theraband
0.40 (−0.51 to 1.31)
−1.47 (–4.69 to 1.75) −0.04 (−0.77 to 0.68)
−0.22 (−0.47 to 0.04) −0.14 (−0.43 to 0.16) −0.31 (−1.37 to 0.74)
−4.17 (−10.69 to −2.35) −5.60 (−10.74 to −0.46)
−12.70 (−23.55 to −1.85) −18.51 (−29.04 to −7.98)
−4.21 (−7.44 to −0.98) −5.63 (−10.09 to −1.17)
−1.55 (–3.56 to 0.46) −1.49 (–4.24 to 1.26)
−0.49 (–4.71 to 3.74) 0.26 (−1.62 to 2.13)
2.79 (−0.88 to 6.47) 1.15 (−2.74 to 5.03)
Adjusted Group Difference Dexterity Theraband
0.48
0.48 0.91
0.24 0.48 0.62
0.38 0.11
0.1 0.02
0.1 0.1
0.27 0.46
0.87 0.87
0.26 0.55
p-value*
0.50
0.20 0.12
0.56 0.23 0.29
0.43 0.71
0.76 1.18
0.93 0.91
0.23 0.36 0.10 0.10 0.49 0.44
Cohen’s d
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0.02 0.02 0.03
1.11 ± 1.76 (0.26 to 1.95)
0.80 ± 1.27 (0.18 to 1.40)
p-value+
1.26 ± 1.85 (0.37 to 2.16)
Change (t1-t0)
Dexterity training group n = 19
0.16 ± 1.80 (−0.71 to 1.03)
0.53 ± 1.95 (−0.42 to 1.47)
0.63 ± 1.46 (−0.07 to 1.34)
Change (t1-t0)
Theraband training group n = 19
0.71
0.3
0.17
p-value#
−0.63 (−1.66 to 0.40)
−0.58 (−1.80 to 0.65)
−0.63 (−1.73 to 0.47)
Group Difference Dexterity - Theraband
−0.89 (−1.79 to 0.05)
−0.60 (−1.72 to 0.53)
−0.81 (−1.85 to 0.24)
Adjusted Group Difference Dexterity Theraband
0.16
0.46
0.27
p-value*
0.41
0.31
0.38
Cohen’s d
Values are mean ± SD or as otherwise indicated; n: number of patients; sec: seconds; CRT: Coin Rotation Task; 9HPT: Nine Hole Peg Test; AFT: Arm Function Training; CAHAI: Chedoke Arm and Hand Activity Inventory; Dexterity Q: Dexterity questionnaire; ¶n=18 (One patient could not perform the CRT on the right side due to severe dexterous difficulties); +p-value change baseline to program end Dexterity training group; #p-value change baseline to program end Theraband training group; *p-value change baseline to program end Dexterity training vs. Theraband training group; d: Cohen’s d. Adjusted Group Difference Dexterity – Theraband: This is the difference in the change of the outcome measure between both groups (Dexterity – Theraband group) controlled for the baseline value of the corresponding outcome measure.
Meals and kitchen Everyday tasks Television and radio
Table 3. (Continued)
CP Kamm, HP Mattle et al.
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Multiple Sclerosis Journal program. This is underlined by the calculated effect sizes (Cohen’s d) which were in favor of the dexterity training program (Table 3). The efficacy of the training program is remarkable, especially with regard to its practicability. Questioning patients and performing the CRT and/or 9HPT as dexterity assessments identifies patients suitable for training. The instruction is restricted to the explanation of the training program and takes 15–30 minutes, which can be done by an occupational or physical therapist. Further time-consuming individualized evaluations and instructions such as in “client-centered” rehabilitation programs are not necessary.33 The home-based training program allows frequent training independently of available hospital or community-based programs, at any time of the day. Patients with problems in transportation and patients who are inflexible time-wise, for example due to work, are able to perform the program as well. Finally, it is very cheap, with material costs below 10 Euros/ Dollars besides the staff costs for the instruction, and materials can be easily accessed in any hardware store. It can be applied as exclusive therapy or integrated in a multimodal therapeutic approach addressing several disabilities of MS patients in stationary, ambulatory or home-based training programs.34 Study limitations We did not evaluate the long-term effect of the training programs. Based on similar studies one can expect that positive effects are maintained for weeks to months without further training.35 However, designing training programs that evidentially improve manual dexterity over a long period of time would be of great interest and importance. Comparisons with control groups without training are problematic because they do not account for the placebo effect of any intervention, and were therefore not incorporated in the randomized controlled study. However, in an independent unmatched group of nine patients with MS that did not perform a training program, we found no significant differences for the all performed endpoints (CRT, 9HPT, JAMAR, dexterity group exercises 1–4, dexterity questionnaire) within an interval of 4 weeks. Although we expect the dexterity questionnaire to be sensitive in detecting changes over time, its responsiveness has to be defined in future studies. Finally, adherence and performance of the exercises was not sufficiently controlled, which is important – however, difficult – in home-based training programs. It could be achieved by self-performed video recordings by patients at home, which is, however, expensive and cumbersome.
Conclusions The standardized 4-week home-based dexterity training program significantly improved manual dexterity and dexterity-related ADL in moderately disabled MS patients with subjectively and objectively impaired manual dexterity. It can be easily applied and performed independently of hospital or communitybased training programs, as well as in patients with transportation problems and time-wise inflexible patients. Therefore, it should be considered in MS patients with impaired manual dexterity. Conflict of interest None declared. Funding The study was supported by a research grant of Bayer (Schweiz) AG.
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